The proposed work will focus on investigating the biological significance of and molecular mechanisms involved in three bacteriophage T4-induced modifications of the host nucleoids: (1) unfolding of the "folded genome" of E. coli, (2) "nuclear disruption", and (3) degradation of the host DNA mononucleotides. Major emphasis will be placed on determining what, if any, effect these virus-induced modifications of the functional host nucleoid have on the arrest of host DNA, RNA, and protein synthesis. We have isolated mutants deficient in each of these processes and have constructed multiple mutants which fail to carry out all or any combination of these processes. We have also identified a wild-type strain of E. coli in which nuclear disruption is essential; this restrictive host will be used to investigate the role of the gene-product responsible for nuclear disruption during the lytic infection. Hopefully, these studies of pre-early virus-host interactions will provide information on the mechanism by which viruses take control of the metabolic machinery of host cells. BIBLIOGRAPHIC REFERENCES: Koerner, J.F., D.P. Snustad, and H.R. Warner (1976). "Membrane associated metabolic systems induced by bacteriophage T4 infection of Escherichia coli." In Membrane-Bound Enzymes (A. Martonosi, ed.). Plenum Press, in press. Snustad, D.P., M.A. Tigges, K.A. Parson, C.J.H. Bursch, F.M. Caron, J.F. Koerner, and D.J. Tutas (1976). Identification and preliminary characterization of a mutant defective in the bacteriophage T4-induced unfolding of the Escherichia coli nucleoid. J. Virology 17: 622-641.